Rapid translocation of nanoparticles from the lung airspaces to the body

Nano-size particles show promise for pulmonary drug delivery, yet their behavior after deposition in the lung remains poorly understood. In this study, a series of near-infrared (NIR) fluorescent nanoparticles were systematically varied in chemical composition, shape, size and surface charge, and their biodistribution and elimination were quantified in rat models after lung instillation. We demonstrate that nanoparticles with hydrodynamic diameter (HD) less than ≈34 nm and a noncationic surface charge translocate rapidly from the lung to mediastinal lymph nodes. Nanoparticles of HD < 6 nm can traffic rapidly from the lungs to lymph nodes and the bloodstream, and then be subsequently cleared by the kidneys. We discuss the importance of these findings for drug delivery, air pollution and carcinogenesis

Gender and age differences among current smokers in a general population survey

BACKGROUND: Evidence suggests a higher proportion of current smokers among female than among male ever smokers at the age above 50. However, little is known about the proportion of current smokers among ever smokers in old age groups with consideration of women in comparison to men from general population samples. The goal was to analyze the proportions of current smokers among female and among male ever smokers including those older than 80. METHODS: Cross-sectional survey study with a national probability household sample in Germany. Data of 179,472 participants aged 10 or older were used based on face-to-face in-home interviews or questionnaires. The proportions of current smokers among ever smokers were analyzed dependent on age, age of onset of smoking and cigarettes per day including effect modification by gender. RESULTS: Proportions of current smokers tended to be larger among female than among male ever smokers aged 40 or above. Women compared to men showed adjusted odds ratios of 1.7 to 6.9 at ages 40 to 90 or older in contrast to men. No such interaction existed for age of onset of smoking or cigarettes per day. CONCLUSION: Special emphasis should be given to current smokers among the female general population at the age of 40 or above in public health intervention

Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate

Purpose: Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate

Organometallic neptunium(III) complexes

Studies of transuranic organometallic complexes provide a particularly valuable insight into covalent contributions to the metal–ligand bonding, in which the subtle differences between the transuranium actinide ions and their lighter lanthanide counterparts are of fundamental importance for the effective remediation of nuclear waste. Unlike the organometallic chemistry of uranium, which has focused strongly on UIII and has seen some spectacular advances, that of the transuranics is significantly technically more challenging and has remained dormant. In the case of neptunium, it is limited mainly to NpIV. Here we report the synthesis of three new NpIII organometallic compounds and the characterization of their molecular and electronic structures. These studies suggest that NpIII complexes could act as single-molecule magnets, and that the lower oxidation state of NpII is chemically accessible. In comparison with lanthanide analogues, significant d- and f-electron contributions to key NpIII orbitals are observed, which shows that fundamental neptunium organometallic chemistry can provide new insights into the behaviour of f-elements

Peri-conceptual and mid-pregnancy drinking:a cross-sectional assessment in two Scottish health board areas using a 7-day Retrospective Diary

Aims: The aim of this study was to evaluate the use of a 7-day Retrospective Diary to assess peri-conceptual and mid-pregnancy alcohol consumption. Background: Alcohol consumption among women has increased significantly and is of international concern. Heavy episodic (‘binge’) drinking is commonplace and is associated with unintended pregnancy. Pre-pregnancy drinking is strongly associated with continued drinking in pregnancy. Routine antenatal assessment of alcohol history and current drinking is variable; potentially harmful peri-conceptual drinking may be missed if a woman reports low or no drinking during pregnancy. Design: Cross-sectional study (n=510) in two Scottish health board areas. Methods: Face-to-face Retrospective Diary administration from February to June 2015 assessing alcohol consumption in peri-conceptual and mid-pregnancy periods. Women were recruited at the mid-pregnancy ultrasound clinic. Results: Of 510 women, 470 (92·0%) drank alcohol before their pregnancy; 187 (39·9%) drank every week. Retrospective assessment of peri-conceptual consumption identified heavy episodic drinking (more than six units on one occasion) in 52·2% (n=266); 19·6% (n=100) reported drinking more than 14 units per week, mostly at the weekend; ‘mixing’ of drinks was associated with significantly higher consumption. While consumption tailed off following pregnancy recognition, 5·5% (n=28) still exceeded the recommended daily two-unit limit in pregnancy. Multivariable logistic regression identified that women who ‘binged’ peri-conceptually were 3·2 times more likely to do this. Conclusion: Statistically significant peri-conceptual consumption levels suggest a substantial proportion of alcohol-exposed pregnancies before pregnancy recognition. Not taking a detailed alcohol history, including patterns of consumption, will result in under-detection of alcohol-exposed pregnancies. The Retrospective Diary offers practitioners a detailed way of enquiring about alcohol history for this population

The impact of radiotherapy late effects on quality of life in gynaecological cancer patients

The aims of this study were to assess changes in quality of life (QoL) scores in relation to radical radiotherapy for gynaecological cancer (before and after treatment up to 3 years), and to identify the effect that late treatment effects have on QoL. This was a prospective study involving 225 gynaecological cancer patients. A QoL instrument (European Organisation for the Research and Treatment of Cancer QLQ-C30) and late treatment effect questionnaire (Late Effects Normal Tissues – Subjective Objective Management Analysis) were completed before and after treatment (immediately after radiotherapy, 6 weeks, 12, 24 and 36 months after treatment). Most patients had acute physical symptoms and impaired functioning immediately after treatment. Levels of fatigue and diarrhoea only returned to those at pre-treatment assessment after 6 weeks. Patients with high treatment toxicity scores had lower global QoL scores. In conclusion, treatment with radiotherapy for gynaecological cancer has a negative effect on QoL, most apparent immediately after treatment. Certain late treatment effects have a negative effect on QoL for at least 2 years after radiotherapy. These treatment effects are centred on symptoms relating to the rectum and bowel, for example, diarrhoea, tenesmus and urgency. Future research will identify specific symptoms resulting from late treatment toxicity that have the greatest effect on QoL; therefore allowing effective management plans to be developed to reduce these symptoms and improve QoL in gynaecological cancer patients

The Nanostructure of Myoendothelial Junctions Contributes to Signal Rectification between Endothelial and Vascular Smooth Muscle Cells

Micro-anatomical structures in tissues have potential physiological effects. In arteries and arterioles smooth muscle cells and endothelial cells are separated by the internal elastic lamina, but the two cell layers often make contact through micro protrusions called myoendothelial junctions. Cross talk between the two cell layers is important in regulating blood pressure and flow. We have used a spatiotemporal mathematical model to investigate how the myoendothelial junctions affect the information flow between the two cell layers. The geometry of the model mimics the structure of the two cell types and the myoendothelial junction. The model is implemented as a 2D axi-symmetrical model and solved using the finite element method. We have simulated diffusion of Ca2+ and IP3 between the two cell types and we show that the micro-anatomical structure of the myoendothelial junction in itself may rectify a signal between the two cell layers. The rectification is caused by the asymmetrical structure of the myoendothelial junction. Because the head of the myoendothelial junction is separated from the cell it is attached to by a narrow neck region, a signal generated in the neighboring cell can easily drive a concentration change in the head of the myoendothelial protrusion. Subsequently the signal can be amplified in the head, and activate the entire cell. In contrast, a signal in the cell from which the myoendothelial junction originates will be attenuated and delayed in the neck region as it travels into the head of the myoendothelial junction and the neighboring cell

Nucleolar Localization of GLTSCR2/PICT-1 Is Mediated by Multiple Unique Nucleolar Localization Sequences

The human glioma tumor suppressor candidate region 2 gene product, GLTSCR2, also called ‘protein interacting with carboxyl terminus 1’ (PICT-1), has been implicated in the regulation of two major tumor suppressor proteins, PTEN and p53, and reported to bind the membrane-cytoskeleton regulator of cell signaling, Merlin. PICT-1 is a nucleolar protein, conserved among eukaryotes, and its yeast homolog has been functionally associated with ribosomal RNA processing. By means of confocal microscopy of EGFP and myc-tagged PICT-1 fusion proteins, we delineate that the nucleolar localization of PICT-1 is mediated by two independent nucleolar localization sequences (NoLS). Unlike most NoLSs, these NoLSs are relatively long with flexible boundaries and contain arginine and leucine clusters. In addition, we show that PICT-1 exhibits a nucleolar distribution similar to proteins involved in ribosomal RNA processing, yet does not colocalize precisely with either UBF1 or Fibrillarin under normal or stressed conditions. Identification of the precise location of PICT-1 and the signals that mediate its nucleolar localization is an important step towards advancing our understanding of the demonstrated influence of this protein on cell fate and tumorigenesis

Variability of wavefront aberration measurements in small pupil sizes using a clinical Shack-Hartmann aberrometer

BACKGROUND: Recently, instruments for the measurement of wavefront aberration in the living human eye have been widely available for clinical applications. Despite the extensive background experience on wavefront sensing for research purposes, the information derived from such instrumentation in a clinical setting should not be considered a priori precise. We report on the variability of such an instrument at two different pupil sizes. METHODS: A clinical aberrometer (COAS Wavefront Scienses, Ltd) based on the Shack-Hartmann principle was employed in this study. Fifty consecutive measurements were perfomed on each right eye of four subjects. We compared the variance of individual Zernike expansion coefficients as determined by the aberrometer with the variance of coefficients calculated using a mathematical method for scaling the expansion coefficients to reconstruct wavefront aberration for a reduced-size pupil. RESULTS: Wavefront aberration exhibits a marked variance of the order of 0.45 microns near the edge of the pupil whereas the central part appears to be measured more consistently. Dispersion of Zernike expansion coefficients was lower when calculated by the scaling method for a pupil diameter of 3 mm as compared to the one introduced when only the central 3 mm of the Shack – Hartmann image was evaluated. Signal-to-noise ratio was lower for higher order aberrations than for low order coefficients corresponding to the sphero-cylindrical error. For each subject a number of Zernike expansion coefficients was below noise level and should not be considered trustworthy. CONCLUSION: Wavefront aberration data used in clinical care should not be extracted from a single measurement, which represents only a static snapshot of a dynamically changing aberration pattern. This observation must be taken into account in order to prevent ambiguous conclusions in clinical practice and especially in refractive surgery